Janis Gonzalez-Martinez

Genetic origins of social networks in rhesus macaques

Sociality is believed to have evolved as a strategy for animals to cope with their environments. Yet the genetic basis of sociality remains unclear. Here we provide evidence that social network tendencies are heritable in a gregarious primate. The tendency for rhesus macaques, Macaca mulatta, to be tied affiliatively to others via connections mediated by their social partners - analogous to friends of friends in people - demonstrated additive genetic variance. Affiliative tendencies were predicted by genetic variation at two loci involved in serotonergic signalling, although this result did not withstand correction for multiple tests. Aggressive tendencies were also heritable and were related to reproductive output, a fitness proxy. Our findings suggest that, like humans, the skills and temperaments that shape the formation of multi-agent relationships have a genetic basis in nonhuman primates, and, as such, begin to fill the gaps in our understanding of the genetic basis of sociality.

Direct effects of leptin on mouse reproductive function: regulation of follicular, oocyte, and embryo development.

Abstract Because body condition can affect reproduction, research has focused on the role of leptin, a body condition signal, in regulation of reproductive function. Objectives of this study were to determine if leptin supplementation directly affects 1) ovarian follicle growth and function, 2) oocyte maturation, or 3) preimplantation embryo development. Follicles cultured in the presence of recombinant mouse leptin resulted in a significant decrease in rate of follicle, but not oocyte, growth in a dose-dependent manner, with higher doses of leptin inhibiting growth. Leptin was also found to significantly increase stimulated progesterone, estradiol, and testosterone production/secretion by cultured follicles in a dose-dependent manner, with higher concentrations of leptin significantly increasing steroidogenesis. Culture of fully grown cumulus-enclosed germinal vesicle-intact (GV) mouse oocytes in the presence of increasing concentrations of leptin (0, 12.5, 25, 50, 100 ng/ml) had no effect on germinal vesicle breakdown (GVBD) or development to metaphase II (MII). Similarly, fully grown denuded oocytes showed no difference in GVBD at any concentration of leptin. However, maturation of denuded oocytes with 100 ng/ml leptin resulted in significantly reduced development to MII compared with oocytes matured with 0 or 12.5 ng/ml leptin. Culture of one-cell mouse embryos in increasing concentrations of leptin had no effect on cleavage or blastomere degeneration at 24 h of culture. Exposure of embryos for the first 96 h of development to increasing concentrations of leptin did not significantly affect total or expanded blastocyst development or hatching of blastocysts from zona pellucida. These results indicate leptin directly enhances insulin and gonadotropin-stimulated ovarian steroidogenesis, compromises denuded oocyte maturation, yet has no direct effect on preimplantation embryo development.

Apoptotic Genes are Differentially Expressed in Aged Gingival Tissue

Cellular and molecular changes of the periodontium associated with a higher prevalence of oral diseases (e.g., chronic periodontitis) in aged populations have received little attention. Since impaired apoptosis during aging appears to be related to chronic inflammatory disorders, we hypothesized that the expression of genes associated with apoptotic processes are altered in aged healthy and periodontitis-affected gingival tissue. Ontology analysis of 88 genes related to apoptotic pathways was performed in gingival biopsies of healthy and periodontitis sites from young, adult, and aged non-human primates (Macaca mulatta), using the GeneChip® Rhesus Macaque Genome Array. Lower expression of anti-apoptotic and higher expression of pro-apoptotic genes were associated with healthy gingival tissue from young compared with aged animals. Few differences in gene expression were observed in healthy gingival tissue between adult and aged animals. Comparison between healthy and periodontitis gingival tissues showed that the up- or down-regulated apoptotic genes in diseased gingival tissue are different in adults compared with aged animals. These results suggest that apoptotic events normally occurring in gingival tissues could be reduced in aging,and unique aspects of apoptotic pathways are potentially involved in the pathophysiology of perio-dontal disease in adult vs. aged gingival tissues.

Personality Traits in Rhesus Macaques (Macaca mulatta) Are Heritable but Do Not Predict Reproductive Output

There is growing evidence that behavioral tendencies, or “personalities,” in animals are an important aspect of their biology, yet their evolutionary basis is poorly understood. Specifically, how individual variation in personality arises and is subsequently maintained by selection remains unclear. To address this gap, studies of personality require explicit incorporation of genetic information. Here, we explored the genetic basis of personality in rhesus macaques by determining the heritability of personality components and by examining the fitness consequences of those components. We collected observational data for 108 adult females living in three social groups in a free-ranging population via focal animal sampling. We applied principal component analysis to nine spontaneously occurring behaviors and identified six putative personality components, which we named Meek, Bold, Aggressive, Passive, Loner, and Nervous. All components were repeatable and heritable, with heritability estimates ranging from 0.14 to 0.35. We found no evidence of an association with reproductive output, measured either by infant survival or by interbirth interval, for any of the personality components. This finding suggests either that personality does not have fitness-related consequences in this population or that selection has acted to reduce fitness-associated variation in personality.

Comparative analysis of gingival tissue antigen presentation pathways in ageing and periodontitis

AIM Gingival tissues of periodontitis lesions contribute to local elevations in mediators, including both specific T cell and antibody immune responses to oral bacterial antigens. Thus, antigen processing and presentation activities must exist in these tissues to link antigen-presenting cells with adaptive immunity. We hypothesized that alterations in the transcriptome of antigen processing and presentation genes occur in ageing gingival tissues and that periodontitis enhances these differences reflecting tissues less capable of immune resistance to oral pathogens. MATERIALS AND METHODS Rhesus monkeys (n = 34) from 3 to 23 years of age were examined. A buccal gingival sample from healthy or periodontitis sites was obtained, total RNA isolated, and microarray analysis was used to describe the transcriptome. RESULTS The results demonstrated increased transcription of genes related to the MHC class II and negative regulation of NK cells with ageing in healthy gingival tissues. In contrast, both adult and ageing periodontitis tissues showed decreased transcription of genes for MHC class II antigens, coincident with up-regulation of MHC class I-associated genes. CONCLUSION These transcriptional changes suggest a response of healthy ageing tissues through the class II pathway (i.e. endocytosed antigens) and altered responses in periodontitis that could reflect host-associated self-antigens or targeting cytosolic intracellular microbial pathogens.

Maculas, monkeys, models, AMD and aging.

Age related macular degeneration (AMD) signs may be found reliably in monkeys (Macaca mulatta) bred selectively in Florida after 14 generations of inbreeding in a closed colony at the University of Puerto Rico. Progression, ultrastructure and functional losses are parallel to those found in humans.

Effects of in vitro maturation and age on oocyte quality in the rhesus macaque Macaca mulatta

OBJECTIVE To evaluate oocyte quality in a primate model. DESIGN Analysis of oocyte karyotype by chromosome spreading and oocyte spindles by confocal microscopy. SETTING Research laboratory, Caribbean Primate Research Center. ANIMAL(S) Rhesus macaques aged 6-22 years. INTERVENTION(S) Fourteen females underwent both Regimen A (FSH + hCG) and Regimen B (FSH only) stimulation cycles to facilitate collection of mature and immature oocytes. Immature oocytes from Regimens A and B underwent in vitro maturation (IVM) to produce metaphase II oocytes. All metaphase II oocytes underwent gradual fixation to spread chromosomes or were fixed and stained with probes specific to alpha-tubulin, actin, and DNA for visualization of the meiotic spindle using confocal microscopy. MAIN OUTCOME MEASURE(S) Karyotype and meiotic spindle architecture differences among in vivo matured (IVO) and IVM oocytes from young and old rhesus macaques. RESULT(S) In all, 4.7% of IVO oocytes (Regimen A) from young females were hyperhaploid versus 25.0% of IVM oocytes (Regimen B) from old females; 4.5% of IVO oocytes (Regimen A) from young females versus 51.5% of IVM oocytes (Regimen B) from old females displayed abnormal chromosome alignment on the metaphase spindle. CONCLUSION(S) IVM can induce meiotic anomalies in macaque oocytes, especially those obtained from older females. Results from this study provide possible explanations for the reported reduction in developmental competence of IVM primate oocytes.

Effects of aging in the expression of NOD‐like receptors and inflammasome‐related genes in oral mucosa

The molecular changes underlying the higher risk of chronic inflammatory disorders during aging remain incompletely understood. Molecular variations in the innate immune response related to recognition and interaction with microbes at mucosal surfaces could be involved in aging-related inflammation. We developed an ontology analysis of 20 nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) and seven inflammasome-related genes (IRGs) in healthy and inflamed/periodontitis oral mucosal tissues from young, adolescent, adult, and aged non-human primates (Macaca mulatta) using the GeneChip(®) Rhesus Macaque Genome array. Validation of some of the significant changes was done by quantitative reverse transcription-polymerase chain reaction. The expression of NLRB/NAIP, NLRP12, and AIM2 increased with aging in healthy mucosa whereas NLRC2/NOD2 expression decreased. Although higher expression levels of some NLRs were generally observed with periodontitis in adult mucosal tissues (e.g. NLRB/NAIP, NLRP5, and NLRX1), various receptors (e.g. NLRC2/NOD2 and NLRP2) and the inflammasome adaptor protein ASC, exhibited a significant reduction in expression in aged periodontitis tissues. Accordingly, the expression of NLR-activated innate immune genes, such as HBD3 and IFNB1, was impaired in aged but not adult periodontitis tissues. Both adult and aged tissues showed significant increase in interleukin-1β expression. These findings suggest that the expression of a subset of NLRs appears to change with aging in healthy oral mucosa, and that aging-related oral mucosal inflammation could involve an impaired regulation of the inflammatory and antimicrobial response associated with downregulation of specific NLRs and IRGs.

Demographic variability and density-dependent dynamics of a free-ranging rhesus macaque population

Density‐dependence is hypothesized as the major mechanism of population regulation. However, the lack of long‐term demographic data has hampered the use of density‐dependent models in nonhuman primates. In this study, we make use of the long‐term demographic data from Cayo Santiagos rhesus macaques to parameterize and analyze both a density‐independent and a density‐dependent population matrix model, and compare their projections with the observed population changes. We also employ a retrospective analysis to determine how variance in vital rates, and covariance among them, contributed to the observed variation in long‐term fitness across different levels of population density. The population exhibited negative density‐dependence in fertility and the model incorporating this relationship accounted for 98% of the observed population dynamics. Variation in survival and fertility of sexually active individuals contributed the most to the variation in long‐term fitness, while vital rates displaying high temporal variability exhibited lower sensitivities. Our findings are novel in describing density‐dependent dynamics in a provisioned primate population, and in suggesting that selection is acting to lower the variance in the population growth rate by minimizing the variation in adult survival at high density. Because density‐dependent mechanisms may become stronger in wild primate populations due to increasing habitat loss and food scarcity, our study demonstrates that it is important to incorporate variation in population size, as well as demographic variability into population viability analyses for a better understanding of the mechanisms regulating the growth of primate populations. Am. J. Primatol. 75:1152–1164, 2013.

B-Virus and Free-Ranging Macaques, Puerto Rico

In Puerto Rico, risk for transmission of B-virus from free-ranging rhesus monkeys to humans has become a serious challenge. An incident with an injured rhesus monkey, seropositive for B-virus, resulted in inappropriate administration of antiviral postexposure prophylaxis. This incident underscores the importance of education about risks associated with interactions between humans and nonhuman primates.